Highlight Publication August 2008

Axe AL#, Walker SA#, Manifava M, Chandra P, Roderick HL, Habermann A, Griffiths G, Ktistakis NT (2008)
Autophagosome formation from membrane compartments enriched in phosphatidylinositol 3-phosphate and dynamically connected to the endoplasmic reticulum.
Journal of Cell Biology 182 685-701
http://dx.doi.org/10.1083/jcb.200803137

Comments on this paper:
Simonsen A, Stenmark H (2008) Self-eating from an ER-associated cup.
Journal of Cell Biology 182 621-622
http://dx.doi.org/10.1083/jcb.200807061

Lay description

When cells find themselves in an environment poor in nutrients they respond by digesting their own proteins to generate amino-acids and other molecules that will allow them to survive until nutrient conditions improve. This starvation response is called autophagy (from the greek for self-eating). In addition to nutrient stress, autophagy is also important for elimination of damaged organelles as a result of ageing, and it is a critical factor that determines survivability of cancer cells.

In order to capture and deliver proteins for digestion during autophagy, a new organelle is formed called the autophagosome which is unusual in that it forms de-novo in the cells and consists of a double membrane outer layer. Two unsolved questions in autophagy concern the origin of the autophagosomal membrane and its mechanism of formation.

In this work we have provided some clues that may help to answer these questions on the origin of autophagosomes. Using high resolution live cell imaging and confocal microscopy we followed the earliest events of autophagosome formation. We found that at least some autophagosomes are formed in novel membrane compartments that we term “omegasomes”. These omegasomes are dynamically connected to the endoplasmic reticulum and are rich in a simple lipid, phosphatidylinositol 3-phosphate. We believe that synthesis of this lipid in response to starvation is a critical early signal that allows autophagosomes to form. Moreover, we think that this lipid also helps in the final stage of autophagosome formation, which is the sealing of the membrane layers.

#About the joint lead authors

Elizabeth Axe

Liz obtained her undergraduate Biochemistry degree at the University of Leicester, then pursued a PhD in Nick Ktistakis' group in the Institute.  She worked on characterising the novel protein DFCP1 and its role in the autophagic pathway.  She completed her PhD in 2006 and has since left lab-bench science to study medicine at King's College London.

Simon Walker

Simon obtained his first degree in Biochemistry at Heriot-Watt University in Edinburgh before moving to the John Innes Centre in Norwich where he studied for his PhD looking at the role of calcium signalling during legume symbiosis.  Simon then worked as a post doc for four years in Peter Cullen's lab at Bristol University investigating the GAP1 family of ras GTPase-activating proteins.  Simon moved to the Babraham Institute in 2004 where he manages the imaging facility.